 Type 1 hypersensitivity reaction also known as immediate hypersensitivity reaction or IgE mediated hypersensitivity reaction because IgE antibody is the main mediator of this hypersensitivity reaction or in common terms also known as allergy. It is the most common type of hypersensitivity reaction to an external antigen which is also known as allergen because the body gets sensitized to this antigen and produces allergy so that antigen also known as allergen. So what is this type 1 hypersensitivity reaction? So the key terms here are that it is a hypersensitivity reaction in a previously sensitized individual and when there is subsequent exposure to this allergen there is rapid immunological reaction to this allergen. So one is the sensitization aspect. So what is this sensitization? How the person gets sensitized to the allergen that is the one aspect of a type 1 hypersensitivity reaction and then what are the responses that is the rapid immunological responses. So basically here the immune system is doing its job normally only however the responses become too much exaggerated. So what happens basically when there is exposure to an antigen which the person is susceptible to. So this susceptibility is determined genetically. So it's not that the allergen acts as an allergen to all the people of the world. Genetically there is susceptibility to that particular antigen and that's why allergy is seen in some individuals and not in other individuals. So when this antigen enters into the body just like the response to any other antigen what happens this antigen is recognized by antigen presenting cells and these antigen presenting cells are macrophages and what are the next antigen presenting cells? Dendritic cells. So these are the main antigen presenting cells. Now for any immune response it is important that these antigen presenting cells phagocytose this antigen. So suppose this is the antigen presenting cell and they have phagocytose this antigen this is the antigen they will break it down and create small small fragments of the main big protein. One of these fragments can act as the main antigen and then they present it on their surface by means of major histocompatibility complex. So a portion a fragment of this main protein is presented to other cells that is the T helper cells. So suppose this is the T helper cell and T helper cell here we are talking and not cytotoxic T cell because it is the activation of T helper cell which is important for activation of other immunity as well. So cytotoxic immunity and activation of the B cell everything depends on the T helper cell. So when this antigen is presented to T helper cell what happens that this T helper cell can further differentiate into two types that is TH1 type of T helper cells and TH2 type of helper cells and this differentiation depends on the cytokines which are released by these macrophages which are presenting the cell to the T helper cells. So when this macrophage releases a cytokine IL4 interleukin 4 this preferentially causes the differentiation of T helper cells to the TH2 type. So that is important because TH1 type actually enhances the cell mediated immunity and TH2 type of helper cell enhance the humoral immunity that is basically by the release of the antibodies by the B cells. So it is this differentiation of T helper cells to the TH2 type of helper cells that is responsible for the type 1 hypersensitivity reaction and remember we are talking only in susceptible people. Now once this TH2 cells form they also release different type of cytokines and major ones of these are interleukin 4 interleukin 5 and interleukin 13. Now this interleukin 4 what it does it is responsible for class switching of B cells class switching that is the B cells are there right which are basically having D antibodies on their surface the antibodies for recognition of the antigen directly. Now this B cell will produce which type of antibody whether it will produce IgG IgM IgE that is known as class switching. So they switch to IgE producing B cells IgE producing B cells okay so this is very important and as I told you before that IgA antibody is the main antibody which is responsible for type 1 hypersensitivity reaction. Actually these IgE antibodies can attach to a particular receptor on mast cell that is FC epsilon receptor so this is mast cell and this is nothing but the receptor for the constant portion of the antibody. See any antibody has two main sides right so suppose this is the IgE antibody this is the constant portion of the IgE antibody and this is the variable binding portion of the IgE antibody which is particular specific for a particular antigen and this constant portion is responsible for the biological properties of the antibodies and this FC part of the IgE antibody binds to this FCE receptor okay so here binds the antibody and obviously there is not a single receptor multiple receptors are there so this mast cell now is bound with many IgE antibodies on its surface. So this is known as sensitization that is with the first exposure of the person to the antigen what has happened that there is differentiation of T cells to TH2 type then there is class switching of the B cells to IgE producing cell and the antibodies which are produced go and bind to the mast cell so this entire thing is known as sensitization when there is subsequent exposure to the antigen now there is increased production or proliferation of this TH2 type of cells and it becomes much more efficient also causing release of the cytokines with now increased production of IgE antibodies so that is one second you see the other cytokines which we were talking this interleukin 5 is responsible for the recruitment of the eocenophils and eocenophils are very important mediators of typhon hypersensitivity reaction as well and this IL 13 interleukin 13 what it does it actually enhances the production of this IgE antibody by the IgE producing B cells so we have more and more IgE production which binds more and more mast cells also you see we talked about that mast cells which already had IgE antibodies bound to it so they will directly recognize the antigen and obviously more and more IgE is also going to bind to these mast so let us see now what will happen when antigen binds to these IgE antibodies which are present on the mast cells so the allergen binds here on the variable portion of the IgE antibody and you see when there is binding on the two or more IgE antibodies what will happen that there is cross linking of these IgE antibodies cross linking and this cross linking is essential for the signal transduction pathways which happen in the mast cell so that will activate the further processes which are responsible for the hypersensitivity reaction so they will be released of the mediators of typhon hypersensitivity from the mast cell and what are these mediators first mast cell has granules and the granule contents will be released so that is known as degranulation so that is the primary mediators of the hypersensitivity reaction and the granule contents includes very important histamine histamine is responsible for smooth muscle contraction right then there is vasodilation and increase in the vascular permeability increased vascular permeability across so that is why in hypersensitivity reaction the person has difficulty in breathing because the smooth muscle contraction has started maybe the bronchial muscle has contracted depending on where the antigen is present that particular smooth muscle contraction will occur then vasodilation increased vascular permeability what will happen that when there is increase in vascular permeability there will be increase in the fluid loss from the vessels and this will result in edema and vasodilation actually that will promote to continuous blood flow to that particular vessel and thus promoting more and more fluid loss from the vessel then histamine also causes increase in the mucosal secretions so like we see in case of allergic rhinitis what happens that the increased secretions occur in the nose then in the bronchals then in gastric glands there will be increase in mucosal secretion again depending on the site of the exposure then other important content of the granules is the enzymes which are responsible for tissue damage and they also lead to complement activation and this complement activation causes generation of the sub-products of the complement for example C3A, C5A which are chemo tactic so this will recruit other leukocytes to the site of the antigen exposure so you keep this in mind that other leukocytes are also recruited to the site of the antigen exposure and we have seen before that how IL-5 released by TH2 is also recruiting the eocenophils to the site of the exposure we'll come to this a little bit later so that is one aspect the degranulation of the contents of the mass granules then second major component is because of this cross linking and signal transduction pathway there is phospholipase A2 activation phospholipase A2 activation and this causes conversion of the phospholipids on the membrane of the muscles to the arachidonic acid which is responsible for formation of other mediators because different enzymes like cyclooxygenase and 5 lipooxygenase act on this arachidonic acid and lead to the production of different mediators in the coax pathway the major mediator which is produced is prostaglandin D2 and in the lipooxygenase pathway the major mediators produced are LTB4 leukotrin B4 leukotrin C4 and leukotrin D4 so let us see what are the actions of these mediators prostaglandin D2 is responsible for bronchospasm so that will lead to breathing difficulty and it also increases mucous secretion then these leukotrins they are very potent in increasing the vascular permeability especially this leukotrin C4 and D4 what they do is they increase the vascular permeability again increasing the edema and there will be obviously increased blood flow and remember that when there is so much blood flow to a particular area and there is vasodilation what is happening if this continues throughout the body then too much vasodilation will decrease the blood pressure it will decrease the peripheral resistance and it will decrease the blood pressure so it is producing shock like condition if it occurs systemically if it occurs locally then it is enhancing the reactions so increased vascular permeability and again there is bronchospasm caused by these leukotrins and leukotrin B4 actually it is again chemotactic for the various leukocytes that being neutrophil, eosinophils, monocytes so these all come to the site of the reaction so that is the second part of the response which is occurring from the mast cells third there is release of certain cytokines from the mast cells as well and these cytokines are TNF alpha interleukin 1 and interleukin 4 again they lead to chemotaxis of the various leukocytes so you see we have referred to this chemotaxis again and again we talked about the interleukin 5 which is released from the helper 2 cells then there is activation of the complement which recruits leukocytes and there are again cytokines released from the mast cells itself which is responsible for chemotaxis and you see here IL4 IL4 where we talked about we talked about that it is important for T helper cells being differentiated into TH2 type of cells and TH2 type of cells where it causes the B cells to produce in IgE antibodies so you see here what is occurring this is a positive feedback which is occurring so once the reaction starts it goes into positive feedback and the response continues okay so why I was talking again and again of chemotaxis and recruitment of the leukocytes to the site because when we talk about type 1 hypersensitivity reaction actually this hypersensitivity reaction has two phases one is the immediate reaction so if we draw it graphically say suppose x axis shows the time after exposure to the allergen and this is the point of allergen exposure immediately there will be a response that is due to the mast cell responses the degranulation the release of the arachidonic acid metabolites but approximately 2 to 24 hours later there is another reaction which is known as late phase reaction so this is early reaction and this is the late phase reaction so two reaction phases occur that is why I was repeatedly talking about the recruitment of the leukocytes because this late phase reaction occurs due to the recruitment of eocenophils neutrophils basophils monocytes to the site of the antigen exposure and their action ultimately leads to tissue damage okay and remember that this is important clinically because here we saw that what are the mediators mast cells are the mediators and histamine leukotrins are the main mediators so here the drugs like antihistaminate drugs or mast cell inactivators that may help but when the late phase reaction starts then these drugs will not be useful rather we need powerful anti-inflammatory drugs like steroids so that is the clinical significance of knowing this immediate reaction and late phase reaction and one thing before we move that as I told you before that eocenophils are one of the very important effectors of the type 1 hypersensitivity because this eocenophils release proteolytic enzymes and they are the ones causing major tissue damage before ending let us see certain examples of type 1 hypersensitivity now this type 1 hypersensitivity can be of two types that is either it can be localized to a particular area so that is known as local immediate hypersensitivity reaction or there can be systemic reaction that is known as anaphylaxis examples of local immediate hypersensitivity reaction being allergic rhinitis conjunctivitis then there is a bronchial asthma because it is also limited to the airways right so bronchial asthma is one example of local immediate hypersensitivity reaction then there are food allergies which again there is a restriction to the GI tract food allergies so these are examples of local hypersensitivity reaction then skin allergy also like contact with an allergen may be present in soap so that is also example of local immediate hypersensitivity reaction and if you see that this reaction depends on the portal of entry so when localized to the respiratory tract GI tract or on a skin so the response will be local however systemic hypersensitivity reaction occurs when there is either injection of the allergen so it goes into the blood directly or there is ingestion of the antigen and it is absorbed into the bloodstream for example peanut allergies they are example of ingestion of the antigen and the bee sting it is an example of injection of the antigen into the circulation so in these cases what is going to happen that there is obviously same responses are going to occur but they will be widespread throughout the body so as I told you that there will be vasodilation and increase in the permeability of the vessels what it is going to do that it is going to decrease the peripheral resistance and hence that will cause the decreased blood pressure plus there will be widespread edema because the fluid is leaking from the vessels throughout the body and this can lead to death as well because it will quickly lead to laryngeal edema which will obstruct the breathing so it has to be treated on a very urgent basis so that was all about type 1 hypersensitivity reaction thanks for watching the video if you liked it do press the like button share the video with others and don't forget to subscribe to the channel physiology open thank you